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Cross-linking and sequence-specific alkylation of DNA by aziridinylquinones. 3. Effects of alkyl substituents.

Abstract：

:The cytotoxicities and DNA cross-linking abilities of several alkyl-substituted diaziridinylquinones have been investigated. The cytotoxicities were determined in DT-diaphorase-rich (H460 and HT29) and -deficient (H596 and BE) cell lines. It was shown that the cytotoxicities in these cell lines correlated with the relative rates of reduction by the purified human enzyme and with the cross-linking efficiencies. The rates of reduction by DT-diaphorase were more dependent on the structures of the compounds than the reduction potentials, as determined by cyclic voltammetry. A computer model was also used to explain high efficiency of cross-linking and the GNC sequence selectivity of the reduced methyl-substituted diaziridinylquinones.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Hargreaves RH,O'Hare CC,Hartley JA,Ross D,Butler J

doi

10.1021/jm991007y

keywords:

subject

Has Abstract

pub_date

1999-06-17 00:00:00

pages

2245-50

issue

12

eissn

0022-2623

issn

1520-4804

pii

jm991007y

journal_volume

42

pub_type

杂志文章

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